The biological functions and biochemical identity of new antigens on the surface membrane of malaria-infected erythrocytes are being characterized to determine their importance for parasite survival and potential value as immunological or chemotherapeutic targets. Plasmodium falciparum - infected erythrocytes express antigenic knobs on their surface which mediate attachment to venular endotholium, thereby preventing passage of mature infected cells through the spleen. We are attempting to identify the functional (ie. binding) components at these knobs plus knob structural components under and through the erythrocyte membrane. An in vitro model has been developed for the in vivo phenomenon of sequestration of mature parasitized erythrocytes. P. falciparum-infected erythrocytes bind specifically to human umbilical and endothelial cells and to a line of human amelanotic melanoma cells via the surface knobs. Since immune sera are capable of blocking or reversing attachment of infected cells to endothelial or melanoma cell layers we are developing the antibody reagents to attempt to identify the biochemial nature of knob components responsible for binding. Plasmodium knowlesi - infected erythrocytes express on surface variant antigen which changes during chronic infection. The parasites capacity to express different antigens allows it to evade variant-specific immune responses. This antigen has been identified in noncloned and cloned parasites and has been shown to be tightly associated with erythrocyte cytoskeletal components.